title: Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier.
abstract: BACKGROUND
  Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).
  
  
  METHODS
  CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.
  
  
  RESULTS
  Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).
  
  
  CONCLUSIONS
  PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, The Trauma Center at Penn, 3400 Spruce Street, Maloney Building, 5th Floor, Philadelphia, PA 19104, USA. Electronic address: jose.pascual@uphs.upenn.edu.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Pascual
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Murcy
authors.forename: Shenghui
authors.initials: S
authors.lastname: Li
authors.forename: Wanfeng
authors.initials: W
authors.lastname: Gong
authors.forename: Rachel
authors.initials: R
authors.lastname: Eisenstadt
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kumasaka
authors.forename: Carrie
authors.initials: C
authors.lastname: Sims
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
authors.forename: Kevin
authors.initials: K
authors.lastname: Browne
authors.forename: Steve
authors.initials: S
authors.lastname: Allen
authors.forename: Jill
authors.initials: J
authors.lastname: Baren
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects*; D011374:Progesterone / Q000493:pharmacokinetics*; D011372:Progestins / Q000493:pharmacokinetics
chemical_list: D011372:Progestins; D011374:Progesterone
keywords: Blood-brain barrier; Endothelium; Intravital microscopy; Neutrophil; Progesterone; Traumatic brain injury